Prevention of prostate cancer by natural product MDM2 inhibitor GS25: in vitro and in vivo activities and molecular mechanisms. (12th May 2018)

• Record Type: Journal Article
• Authors: Wang, Wei; Qin, Jiang-Jiang; Li, Xin; Tao, Guanyu; Wang, Qiang; Wu, Xuming; Zhou, Jianwei; Zi, Xiaolin; Zhang, Ruiwen
• Is Part Of: Carcinogenesis. Volume 39:Number 8(2018)
• Page Start: 1026
• Page End: 1036
• Publication Date: 2018-05-12
• Subjects: Carcinogenesis -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Cancer -- Prevention -- Periodicals; Cancer -- Periodicals; 616.994071
• DOI: 10.1093/carcin/bgy063
• Languages: English
• ISSNs: 0143-3334

Abstract

Abstract: Prostate cancer remains a major health problem in the USA and worldwide. There is an urgent need to develop novel approaches to preventing primary and metastatic prostate cancer. We have identified 25-OCH3 -protopanaxadiol (GS25), the most active ginsenoside that has been identified so far; it has potent activity against human cancers, including prostate cancer. However, it has not been proven if GS25 could be a safe and effective agent for cancer prevention. In this study, we used the TRAMP model and clearly demonstrated that GS25 inhibited prostate tumorigenesis and metastasis with minimal host toxicity. Mechanistically, GS25 directly bound to the RING domain of MDM2, disrupted MDM2–MDMX binding and induced MDM2 protein degradation, resulting in strong inhibition of prostate cancer cell growth and metastasis, independent of p53 and androgen receptor status. In conclusion, our in vitro and in vivo data support the potential use of GS25 in prevention of primary and metastatic prostate cancer. Abstract : The present study demonstrates the safe and effective applications of GS25 for preventing primary and metastatic prostate cancer, and elucidates that targeting MDM2 is the major mechanism of action.